Chronic neuropsychologic impairment (NPI) is a major complication in HIV infected long-term survivors on antiviral therapy (HAART). The pathogenesis is still unknown but likely candidates are: neurotoxic viral proteins; pharmacologic side effects; behavioral risk factors (e.g. drug abuse); chronic inflammation accompanied by neuroglial activation; the patient genetic background potentially modulating the metabolic and endocrinologic response to infection; age; gender; and also specific opportunistic pathologies. We have now identified a unique patient cohort at the Victor Babes Hospital (VBH) in Bucharest that may help in deciphering some of the specific NP risk factors associated with long term HIV infection. These patients are uniquely qualified for a longitudinal study: they form a highly homogenous cohort (average 18 y. o.) with similar viral strain infection (clade F), HAART regimen (approx. 7 years), and genetic background. We will assemble a cohort of 75 subjects (25 HIV+ with NPI, 25 HIV+ without NPI, and 25 HIV-) that will be studied for 2 years through regular neuromedical and NP exams and clinical laboratory evaluations of serologic and cerebrospinal fluid (CSF) markers of disease. To measure NPI we will use a test battery developed at the HIV Neurobehavioral Research Center (HNRC) at UC San Diego. Specific Aim #1: Demonstrate the cross-cultural applicability in Romania of a comprehensive neuropsychological (NP) test battery that has been extensively validated for detecting and characterizing neurobehavioral effects of HIV-1 infection in the U.S. Specific Aim #2: Identify comorbid factors in the Romanian young adults with HIV and compare them to the degree of NPI. Specific Aim #3: Characterize the neurotoxic potential of the Romanian clade F HIV and its susceptibility to antiviral treatments. This project will demonstrate feasibility and will help develop an infrastructure to perform neurobehavioral and virological studies in Romania, where no systematic studies of the neurocognitive manifestations of HIV-1 have been performed. The Romanian cohort could provide a unique insight in the future of HIV- associated NPI in long term-survivors on HAART. [unreadable] [unreadable] [unreadable]